Abstract
Proteasomal degradation provides the crucial machinery for maintaining cellular proteostasis. The biological origins of modulation or impairment of the function of proteasomal complexes may include changes in gene expression of their subunits, ubiquitin mutation, or indirect mechanisms arising from the overall impairment of proteostasis. However, changes in the physico-chemical characteristics of the cellular environment might also meaningfully contribute to altered performance. This review summarizes the effects of physicochemical factors in the cell, such as pH, temperature fluctuations, and reactions with the products of oxidative metabolism, on the function of the proteasome. Furthermore, evidence of the direct interaction of proteasomal complexes with protein aggregates is compared against the knowledge obtained from immobilization biotechnologies. In this regard, factors such as the structures of the natural polymeric scaffolds in the cells, their content of reactive groups or the sequestration of metal ions, and processes at the interface, are discussed here with regard to their influences on proteasomal function.
Highlights
Proteasomes are unique multisubunit proteolytic complexes that play a critical role in the mechanisms aimed at the maintenance of proteostasis, a critical homeostatic process regulating the mass and localization of proteins [1,2,3,4]
This pathway acts as a non-lysosomal garbage disposal mechanism for damaged, redundant, and misfolded proteins and regulates the levels of many short-lived regulatory proteins related to cellular metabolism and gene expression
These data corroborate the findings that during oxidative stress, the pool of 20S proteasomes expands through their uncoupling from the regulatory complex 19S [116], which has higher susceptibility to oxidation compared to 20S [117], and 20S proteasomal degradation dominates over ubiquitin- and ATP-dependent proteolysis
Summary
Proteasomes are unique multisubunit proteolytic complexes that play a critical role in the mechanisms aimed at the maintenance of proteostasis, a critical homeostatic process regulating the mass and localization of proteins [1,2,3,4]. Taking into account the mixed content of both inducible and constitutive subunits, which has been confirmed in the core particles [28], 36 diverse theoretical subtypes of the 20S proteasomes in total, differing in their specificity and proteolytic capacity, were proposed This number increases further when considering the fact that the 20S can associate with either 19S or 11S, or their combinations, forming a ‘mixed’ type or ‘hybrid’ proteasome, resulting in a variety of patterns in the proteasomal peptide products. A mathematical model suggested that the substrate residence time inside the proteolytic chamber (governed by the gate size of the axial channel) significantly affects the produced fragment length distribution and the proteasome kinetics [39]. The enzymatic activity of proteasomal complexes ubiquitination,inpvhivoosmpahyoberyadladittiioonnal/ldy mepodhuolastepdhboy rpyosltatrtainoslnat,ioonxalimdoadtiifoicnat,ioonsr, snuicthraasttihoenglyocfosaylmatiionn,o acid residues (Tables 2a–e andub3iqau,ibtin,aFtiiogn,uprheos1p)h.orylation/dephosphorylation, oxidation, or nitration of amino acid residues (Tables 2a–e and 3a,b, Figure 1)
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